Background: Previous studies on the systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts, as a prognostic marker in patients with colorectal cancer (CRC) yielded inconsistent results. The aim of this study was to evaluate the prognostic and clinicopathological role of SII in CRC via meta-analysis. Methods: A comprehensive literature survey was performed on PubMed, Web of Science, Embase and the Cochrane Library databases to include studies published up to 6 April 2020. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed to estimate the prognostic and clinicopathological value of SII in CRC. Results: A total of 12 studies published between 2016 and 2019 were included in our meta-analysis. The combined analysis showed that high SII levels were significantly associated with worse overall survival (OS; HR = 1.61, 95% CI = 1.21–2.13, p = 0.001) and progression-free survival (HR = 1.74, 95% CI = 1.26–2.39, p = 0.001) in CRC. Moreover, elevated SII was also correlated with poor tumor differentiation (OR = 1.60, 95% CI = 1.27–2.02, p < 0.001), presence of distant metastasis (OR = 2.27, 95% CI = 1.10–4.67, p = 0.026), ECOG PS of 1–2 (OR = 1.98, 95% CI = 1.39–2.84, p < 0.001) and tumor size ⩾5 cm (OR = 1.49, 95% CI = 1.18–1.88, p = 0.001). However, high SII was not significantly associated with sex, tumor location, lymph node metastasis, or age in patients with CRC. Conclusion: Our meta-analysis indicated that high SII levels predicted poor prognosis in CRC. In addition, an elevated SII was also associated with clinical factors, implying higher malignancy of the disease.

Background: Integrin-mediated platelet-tumor cell contacting plays an important role in promoting epithelial-mesenchymal transition (EMT) transformation of tumor cells and cancer metastasis, but whether it occurs in breast cancer cells is not completely clear. Objective: The purpose of this study was to investigate the role of integrin α2β1 in platelet contacting to human breast cancer cell line MCF-7 and its effect on the EMT and the invasion of MCF-7 cells. Methods: Human platelets were activated by thrombin, and separated into pellets and releasates before the co-incubation with MCF-7 cells. Cell invasion was evaluated by transwell assay. The surface integrins on pellets and MCF-7 cells were inhibited by antibodies. The effect of integrin α2β1 on Wnt-β-catenin pathway was assessed by integrin α2β1-silencing and Wnt-β-catenin inhibitor XAV. The therapeutic effect of integrin α2β1-silencing was confirmed in the xenograft mouse model. Results: Pellets promote the invasion and EMT of MCF-7 cells via direct contacting of surface integrin α2β1. The integrin α2β1 contacting activates Wnt-β-catenin pathway and promotes the expression of EMT proteins in MCF-7 cells. The activated Wnt-β-catenin pathway also promotes the autocrine of TGF-β1 in MCF-7 cells. Both Wnt-β-catenin and TGF-β1/pSmad3 pathways promote the expression of EMT proteins. Integrin α2β1-silencing inhibits breast cancer metastasis in vivo. Conclusions: The direct interaction between platelets and tumor cells exerts its pro-metastatic function via surface integrin α2β1 contacting and Wnt-β-catenin activation. Integrin α2β1-silencing has the potential effect of inhibiting breast cancer metastasis.

Programmed cell death ligand 1 (PD-L1) expression has been shown to associate with poor prognosis in a variety of solid tumors. However, the prognostic value of PD-L1 expression in cervical cancer is still controversial. Therefore, we carried a meta-analysis to investigate the prognostic and clinicopathological impact of PD-L1 in cervical cancer. A comprehensive literature search in was performed in PubMed, Embase, Web of Science, and Cochrane Library. The correlation between PD-L1 expression and overall survival (OS), progression-free survival (PFS), and clinicopathological features was analyzed by hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). Seven studies with 783 patients were included in this meta-analysis. The combined HR and 95% CI of OS was 2.52 (1.09–5.83), p = 0.031. The pooled results for PFS were HR = 2.07, 95% CI = 0.52–8.23, p = 0.302. The results of subgroup analysis showed that PD-L1 was a significant prognostic factor of poor OS in Asian patients (HR = 4.77, 95% CI = 3.02–7.54, p < 0.001) and of poor PFS in Asian patients (HR = 4.78, 95% CI = 1.77–12.91, p = 0.002). However, the pooled results suggested that PD-L1 was not significantly correlated with lymph node metastasis, tumor size, FIGO stage, depth of invasion, lymph-vascular invasion, or age. The results of this meta-analysis suggest that PD-L1 overexpression is related to poor OS in patients with cervical cancer and poor PFS in Asian patients with cervical cancer. This study also suggests that PD-L1 is a promising prognostic indicator for cervical cancer.

Background: Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma.Methods: A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg’s test and Egger’s test.Results: Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57–1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43–1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22–0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90–1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51–1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06–4.83, P = 0.592).Conclusions: This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

Introduction: The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC). Methods: Quantitative real-time PCR (QRT-PCR) and Western blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTT assay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial–mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dual-luciferase reporter assay was performed to confirm the direct target of miR-499a-5p. Results: MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression. Discussion: MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

The prognostic significance of the systemic inflammatory response index (SIRI) in patients with cancer receiving programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely investigated; however, the results have been conflicting. As such, the present meta-analysis aimed to analyze the precise significance of the SIRI in predicting prognosis in patients with cancer undergoing ICI therapy. A comprehensive literature search of the Web of Science, PubMed, Embase, and Cochrane Library databases for relevant studies, published from inception to April 25, 2024, was performed. The SIRI was analyzed for its prognostic utility in patients undergoing ICI therapy by calculating combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Six studies comprising 1133 patients were included in the analysis. Pooled data revealed that a higher SIRI was significantly associated with poor overall survival (OS) (HR 1.96 [95% CI 1.55-2.47]; p < 0.001) and progression-free survival (PFS) (HR 1.41 [95% CI 1.19-1.67]; p < 0.001) for patients who underwent PD-1/PD-L1 ICI treatment. Subgroup analysis revealed that SIRI was markedly associated with dismal OS and PFS, independent of sample size, cut-off value, and survival analysis (p < 0.05). The findings were verified to be robust against publication bias and sensitivity analyses. In summary, an elevated SIRI was significantly associated with OS and PFS in patients with cancer undergoing PD-1/PD-L1 ICI treatment. SIRI may a candidate indicator for predicting the prognosis of patients undergoing ICI therapy.